Renin is a natural enzyme which is released into the blood from the kidney. It cleaves its natural substrate, angiotensinogen, releasing decapeptide, angiotensin I. This is in turn cleaved by converting enzyme in the lung, kidney, and other tissues to an octapeptide, angiotensin II. Angiotensin II raises blood pressure both directly by causing arteriolar construction and indirectly by stimulating release of the sodium-retaining hormone aldosterone from the adrenal gland causing a rise in extracellular fluid volume. Inhibitors of renin have been sought as agents for control of hypertension, congestive heart failure, and hyperaldosteronism.
The present invention concerns certain novel peptides which are selective for inhibition of renin versus related enzymes, especially cathepsin D and which possess potent oral activity. It also concerns pharmaceutical compositions containing these novel peptides, methods of treating renin-associated hypertension, congestive heart failure, hyperaldosteronism, and glaucoma as well as the use of the peptides as diagnostic tools. It also concerns a method for treating diseases caused by retroviruses including HTLV-I, -II, and -III. Methods for preparing the peptides are also disclosed.
U.S. Pat. No. 4,479,941 covers certain renin-inhibitory peptides of the formula ##STR1## The compounds are useful as renin and acid protease inhibitors.
Since HIV protease, like renin, is an aspartyl protease, these compounds can also be used to treat diseases caused by retroviruses including HTLV-I, -II, and -III.